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Antigen-specific regulatory T cells to treat SLE

Description 
Systemic lupus erythematosus (SLE) is an autoimmune disease that causes multi-organ dysfunction, significant morbidity, and requires lifelong global immune suppression. SLE occurs because the immune system becomes misdirected and attacks proteins found within the cell nucleus. Autoreactivity against a particular protein, the Smith (Sm) antigen, is associated with more severe disease manifestations, particularly an increase in lupus nephritis. Experimental evidence demonstrate that autoreactivity to the Sm antigen causes renal failure. Like other autoimmune diseases, there are no antigen-specific therapies. The goal of this project is to develop a treatment that would specifically inhibit the inflammatory immune response against the Sm antigen; and, thus, allow for a significant reduction in the use of non-specific immunosuppression. Recently, we showed that autoantigen-specific regulatory T cells (Tregs) are potent suppressors of autoimmunity and disease. Based on that important find, using new and innovative methods, we have developed the capability to generate autoantigen-specific Tregs that can be adoptively transferred into patients to treat disease. Our process involves: (1) the use of single cell RNA sequencing to identify antigen-specific T cell receptors (TCRs), (2) a high-efficiency lentiviral transduction system for transducing autoantigen-specific TCRs onto Tregs, and (3) an established humanised mouse model of lupus nephritis using patient blood to test the efficiency of the autoantigen-specific Tregs in suppressing human pathogenic autoimmune responses. This work will form the basis of pursuing cell-based clinical trials in SLE; and, importantly, instigate a paradigm shift in the way autoimmune diseases are treated.
Essential criteria: 
Minimum entry requirements can be found here: https://www.monash.edu/admissions/entry-requirements/minimum
Keywords 
regulatory T cells, SLE, autoimmunity
School 
School of Clinical Sciences at Monash Health / Hudson Institute of Medical Research » Medicine - Monash Medical Centre
Available options 
PhD/Doctorate
Masters by research
Honours
Time commitment 
Full-time
Part-time
Top-up scholarship funding available 
No
Physical location 
Monash Health Translation Precinct (Monash Medical Centre)
Co-supervisors 
Assoc Prof 
Alberta Hoi

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